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Effects of MK-801 (dizocilpine) on brain cell membrane function and energy metabolism in experimental Escherichia coli meningitis in the newborn piglet.

By Sun Young Ko, Jae Won Shim, Sung Shin Kim, Mi Jung Kim, Yun Sil Chang, Won Soon Park, Son Moon Shin and Mun Hyang Lee

Abstract

We evaluated the efficacy of non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) as an adjuvant therapy in experimental neonal bacterial meningitis. Meningitis was induced by injecting 10(6) colony forming units of Escherichia coli into the cisterna magna. MK-801 3 mg/kg was given as a bolus intravenous injection, 30 min before the induction of meningitis. MK-801 did not down-modulate the inflammatory parameters, such as increased intracranial pressure, cerebrospinal fluid (CSF) leukocytosis, increased lactate and TNF-alpha levels in the CSF, and hypoglycorrhachia observed in the meningitis group. MK-801 did not significantly attenuate the elevated glutamate concentration in the CSF. However, MK-801 showed some neuroprotective effects as evidenced by significant attenuation of cerebral lipid peroxidation products (conjugated dienes) and increase of brain high-energy phosphate compounds (ATP and PCr). Improvement in cerebral cortical cell membrane Na+, K+ -ATPase activity did not reach a statistical significance. These results suggest that MK-801 was effective in ameliorating brain injury in neonatal bacterial meningitis, although it failed to attenuate the inflammatory responses

Topics: Research Article
Publisher: Korean Academy of Medical Sciences
OAI identifier: oai:pubmedcentral.nih.gov:3055019
Provided by: PubMed Central

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Citations

  1. (1992). Abnormalities of cerebral blood flow in the acute phase of bacterial meningitis in adults.
  2. (1982). Accurate measurement of cerebral energy metabolism in the conscious unrestrained neonatal piglet. Biol Neonate
  3. (1994). Acute bacterial meningitis in the newborn.
  4. (2000). Acute decrease in net glutamate uptake during energy deprivation.
  5. (1993). Amino acids in cerebrospinal and brain interstitial fluid during experimental pneumococcal meningitis. Pediatr Res
  6. (1997). An EPR investigation of the products of the reaction of cytosolic and mitochondrial aconitases with nitric oxide.
  7. (1986). Biological effects of the superoxide radical. Arch Biochem Biophys
  8. (1982). Central sympathomimetic activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo (MK801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev Res
  9. (1992). Cerebrovascular complications of bacterial meningitis in adults. Neurology
  10. (1979). Comparative aspects of the brain growth spurt. Early Hum Dev
  11. (1974). Creatine phosphate.
  12. (1993). Effect of experimental Escherichia coli meningitis on concentrations of excitatory and inhibitory amino acids in the rabbit brain: in vivo microdialysis study. Pediatr Res
  13. (1998). Effect of hyperglycemia on brain cell membrane function and energy metabolism during hypoxia-ischemia in the newborn piglets. Brain Res
  14. (1998). Effects of induced hyperglycemia on brain cell membrane function and energy metabolism during the early phase of experimental meningitis in newborn piglets. Brain Res
  15. (1996). Excess glutamate in the cerebrospinal fluid in bacterial meningitis.
  16. (1987). Excitotoxicity and the NMDA receptor. Trends Neurosci
  17. (1998). Factors affecting excitatory amino acid release following severe human head injury.
  18. (1986). Glutamate and the pathophysiology of hypoxic ischemic brain damage. Ann Neurol
  19. (1988). Glutamate neurotoxicity and diseases of the nervous system. Neuron
  20. (2001). Hypoxic-ischemic encephalopathy: biochemical and physiological aspects, W.B Saunders Company, Neurology of the newborn, fourth Ed.
  21. (1991). Inhibition of sodium-potassium-ATPase: A potentially ubiquitous mechanism contributing to central nervous system neuropathology. Brain Res Rev
  22. (1992). Long-term outcome of neonatal meningitis.
  23. (1990). Loss of cerebrovascular autoregulation in experimental meningitis in rabbits.
  24. Mechanism of brain damage in H. influenzae meningitis.
  25. (1998). Modification of ion homeostasis by lipid peroxidation: Roles in neuronal degeneration and adaptive plasticity. Trends Neurosci
  26. (1999). Near infrared spectroscopic monitoring of secondary cerebral energy failure after transient global hypoxia-ischemia in the newborn piglet. Neurol Res
  27. (1990). Neonatal Gram negative meningitis. A 10-year review, with reference to outcome and relapse of infection.
  28. (1996). Neuroprotective effect of excitatory amino acid antagonist kynurenic acid in experimental bacterial meningitis.
  29. (1995). Neurotransmitters an vulnerability of the developing brain. Brain Dev
  30. (1991). Outer membrane protein A (Omp A) contributes to serum resistance and pathogenicity of Escherichia coli K-1. Infect Immun
  31. (1981). Partial inactivation of Na+, K+-APTase in cortical brain slices in normal Krebs-Ringer phosphate medium at 1 and 10 atm oxygen pressures.
  32. (1985). Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters. Clin Sci
  33. (1996). Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitirite. Circ Res
  34. (1985). Specific ouabain binding to brain microvessels and choroids plexus.
  35. (1984). Spectrophotometric detection of lipid conjugated dienes. Methods Enzymol